Investigations of the pulmonary circulation in man have been among the most difficult to study in terms of human physiology and pathology. Such investigations have generally required invasive techniques which did not lend themselves well to serial hemodynamic studies. This approach in this proposal is to apply non-invasive methods which we have developed in the last several years with the help of previous grant support to establish normal values for them in children and adults at rest, during exercise and with pharmacologic agents. The keystones of the non-invasive methods has been the instantaneous pulmonary capillary blood flow method using the nitrous oxide plethysmographic method and the rebreathing technique method for estimation of diffusing capacity, capillary blood flow, pulmonary tissue volume, oxygen consumption and alveolar volume. In addition to these non-invasive methods, certain invasive methods such as the ether plethysmographic technique for estimation of pulmonary arterial blood volume and interdependence allow study of various experimental disease states in anesthetized dogs. Utilizing the bronchofiberscope, we are now in a position to examine lobar and segmental lung function which should help in the diagnosis of pulmonary emboli, pre-operative assessment of patients with bullous disease and patients undergoing resectional surgery as well as yielding useful physiologic information on the effects of gravity on pulmonary function. It might be possible with methods employed in this grant proposal to indirectly estimate pulmonary arterial pressure and thus study the course of pulmonary hypertension with and without treatment by pharmacologic agents. With experimental models such as water immersion, oleic induced respiratory distress syndrome experimental canine asthma and aspiration pneumonitis, it should be possible to understand the basic physiologic and treatment. Effects of changes in environmental temperature and humidity on pulmonary circulatory parameters should establish useful background information in normal subjects and perhaps give information on the development of asthmatic attacks in children. In summary, the information to be obtained should help in understanding the role of the pulmonary circulation in normal and disease sujects and aid in the pathophyssology and treatment of various pulmonary hypertensive states.